Up-regulation of FOXP3 and induction of suppressive function in CD4+ Jurkat T-cells expressing hepatitis C virus core protein

• Published in: Clinical science (1979) Vol. 123; no. 1-2; pp. 15 - 27
• Main Authors: DOMINGUEZ-VILLAR, Margarita, FERNANDEZ-PONCE, Cecilia, MUNOZ-SUANO, Alba, GOMEZ, Esperanza, RODRIGUEZ-IGLESIAS, Manuel, GARCIA-COZAR, Francisco
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.07.2012
• Subjects: Biological and medical sciences; Blotting, Western; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - virology; CTLA-4 Antigen - metabolism; Electrophoresis, Polyacrylamide Gel; Forkhead Transcription Factors - metabolism; General aspects; Hepacivirus - immunology; Hepatitis C Antigens - metabolism; Hepatitis C, Chronic - immunology; Human viral diseases; Humans; Immunity, Cellular; Infectious diseases; Interleukin-2 - metabolism; Interleukin-2 Receptor alpha Subunit - metabolism; Jurkat Cells; Medical sciences; Real-Time Polymerase Chain Reaction; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - virology; Transduction, Genetic; Up-Regulation; Viral Core Proteins - metabolism; Viral diseases; Viral hepatitis; CD4 T lymphocyte; Induction; Hepatic disease; Immune evasion; Protein; Infection; Virus; Medicine; Immunological surveillance; Regulation(control); CD4; Viral disease; Immune tolerance; T-Lymphocyte; regulatory T-cell; forkhead box P3 (FOXOP3); Digestive diseases; Flaviviridae; Hepatitis C virus; Hepacivirus; Regulatory cell; Transcription factor FOXP3; Viral hepatitis C
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20110631

HCV (hepatitis C virus) infection is a serious health care problem that affects more than 170 million people worldwide. Viral clearance depends on the development of a successful cellular immune response against the virus. Interestingly, such a response is altered in chronically infected patients, leading to chronic hepatitis that can result in liver fibrosis, cirrhosis and hepatocellular carcinoma. Among the mechanisms that have been described as being responsible for the immune suppression caused by the virus, Treg-cells (regulatory T-cells) are emerging as an essential component. In the present work we aim to study the effect of HCV-core protein in the development of T-cells with regulatory-like function. Using a third-generation lentiviral system to express HCV-core in CD4+ Jurkat T-cells, we describe that HCV-core-expressing Jurkat cells show an up-regulation of FOXP3 (forkhead box P3) and CTLA-4 (cytotoxic T-lymphocyte antigen-4). Moreover, we show that HCV-core-transduced Jurkat cells are able to suppress CD4+ and CD8+ T-cell responses to anti-CD3 plus anti-CD28 stimulation.